1. Field of the Invention
This invention relates to the preparation of collagenous tissue. In particular, it relates to prostheses made from collagenous tissue.
2. Description of the Prior Art
Despite significant advances in surgery and medicine, there is still no satisfactory prosthesis available for small arterial replacements (less than 3 mm in diameter). The requirements for an ideal prosthetic material are: 1) biocompatible or non-antigenic; 2) mechanical compatibility or matched elasticity; 3) stability under continuous stress; 4) resistant to thrombosis formation; 5) ease and low cost in fabrication; and 6) ease of sterilization. Unfortunately, there has been no existing man-made prosthesis that meets all these criteria, especially for small-diameter arterial prosthesis such as a graft for coronary artery bypass.
Collagen, the major protein forming the blood vessel and skin of all living organisms, is an ideal material for blood vessel prosthesis with no antigenicity and good elasticity. However, all the previous studies and patents in making collagen prostheses for blood vessel replacements failed to reach a acceptable patency rate (&gt;90%) due to high incidence of thrombosis formation, especially in small-diameter blood vessel. Some examples of the prior art in making collagen prosthesis are set forth in the patents briefly described below.
The U.S. Pat. No. 4,082,507 to Sawyer describes a method to chemically modify collagen surfaces to negative charges and then subsequent tanning with glutaraldehyde. He suggests that negative charged blood flow surface may prevent thrombosis formation. The patency of the negatively charged collagen prostheses is 75% within 10 months (Sawyer P N: Patency of Small-Diameter Negatively Charged Glutaraldehyde-Tanned Grafts, in Sawyer P N (eds):MODERN VASCULAR GRAFTS. New York, McGraw-Hill Book Company, 1987, p 163-180).
The U.S. Pat. No. 4,319,363 to Ketharanathan describes a method to obtain a type I collagen prosthesis. After being subjected to glutaraldehyde tanning, all the prostheses are thrombosed when their diameters are less than 4 mm.
The U.S. Pat. No. 4,597,762 to Walter describes a process and an apparatus to obtain a type I collagen prosthesis with a patency rate of 14% within 4 weeks.
The U.S. Pat. No. 4,776,853 to Klement et al disclosed a process comprised of extracting of a tissue by a series of detergent and enzymatic treatments and storage of the tissue in physiologic buffered solutions.
The U.S. Pat. Nos. 4,787,900 and 4,902,289 to Yannas describe a method for forming a multilayer blood vessel prosthesis with biodegradable material and collagen.
The U.S. Pat. No 4,814,120 to Huc et al introduces a process to prepare collagen gel and subsequently drying the gel to form a collagen tube.
The U.S. Pat. No. 4,990,131 to Dardik et al describes a method of tanning umbilical cord vessels with glutaraldehyde under cyclic pressure so that tanning agent can pass through the media wall.
None of the above patents have fulfilled the requirements for an ideal small-diameter blood vessel prosthesis and achieved an adequate patency rate in small arterial transplantation (less than 3 mm in diameter). The possibilities for their failures to obtain satisfactory patency in small-diameter vascular replacement could be due to following reasons: 1) type I collagen, a thrombogenic protein, was used for the blood flow surface; 2) glutaraldehyde tanning of the blood vessel resulted in decreased vascular elasticity and compliance; 3) enzyme-digesting caused denaturation of elastin and collagen structures; and 4) endothelial and smooth muscle cells acting as antigens were not completely removed from the blood vessel and cause tissue rejection.
The advantages of the present invention include that: 1) high patency rate obtained in an arterial prosthesis with 1.2 mm in diameter, 2) simplicity for fabrication and sterilization; 3) preservation of tissue elasticity and compliance therefore suitable for small-diameter blood vessel implants; and 4) decreased antigenicity with extensive washing that may minimize aneurysm formation and calcification. The procedure can be carried out at room temperature without requirement of accurate pH or other buffers. Sterilization of the graft is achieved by detergent washing and alcohol preservation without requirement of other antibiotic treatments and crosslinking agents.
Use of organic surfactants to treat a heart valvular tissue has been described by several prior patents in an attempt to reduce tissue calcification. The following patents disclosed various techniques to treat tissue with surfactants in combination with glutaraldehyde fixation.
The U.S. Pat. No. 4,323,358 to Lentz and Pollock discloses treatment of glutaraldehyde-fixed tissue with a water-soluble salt of sulfated aliphatic alcohol to reduce tissue calcification.
The U.S. Pat. No. 4,553,974 to Dewanjee discloses a process for the treatment of collagenous tissue with surfactants prior to fixation for a period of 2 to 6 hours in order to promote the growth of endothelial cells.
The U.S. Pat. No. 5,215,541 to Nashef et al discloses treatment of a glutaraldehyde-fixed tissue with a variety of anionic and nonionic surfactants to reduce calcification in a heart valve.
Although calcification was reduced in the procedure described by the prior art disclosures using a subcutaneous model with implantation of a valvular tissue under rat skin, the implanted valve was not under a physiological pressure and had no contact with blood flow. Calcification still occurred as the valves were implanted in the aortic position during long-term implantation (Thubrikar M J, Nolan S P, Deck J D, et al: Intrinsic Calcification of T6-processed and Control Porcine and Bovine Bioprostheses in Calves. Trans Am Soc Artif Intern Organs 1983;24:245-249). Furthermore, none of the aforesaid prior art disclosures recognized the importance of the tissue antigens at cell membrane surface that cause rejection and consequent degeneration of the implanted tissue. All of the above prior art disclosures have used glutaraldehyde to fix the tissue before or after the treatment of surfactants. The disadvantages of glutaraldehyde fixation include: 1) antigenic cell proteins cannot be removed from the tissue after fixation process and 2) there is a decrease in tissue elasticity by fixation that promotes thrombosis and prevents angiogenesis of the tissue. In addition, the duration of surfactant treatment in the above prior art disclosures was usually less than 2 days without any mechanical and alcohol washing.
In the present invention, the biological collagenous tissue is processed by extensive detergent soaking and washing to remove the cellular elements, mainly lipid membrane proteins, and to maintain the mechanical property of the tissue such as compliance, defined as a percentage increase in blood vessel diameter followed by an elevation of the intraluminal pressure, of a blood vessel. The processed tissue is suitable not only for small-diameter blood vessel implants, but also for other tissue implants including heart valve, venous valve, skin and cornea.